Clinical characteristics of Danon disease / 中华心血管病杂志

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

Discordance of Estrogen Receptor,Progesterone Receptor,Cerb-B2,Ki-67 Index and P53 Expressions between Primary and Recurrent or Metastatic Sites in Breast Cancer Patients / 中国医学科学院学报

Objective To approach the discordance of estrogen receptor(ER),progesterone receptor(PR),Cerb-B2,Ki-67 index and P53 expressions between primary and regional or distant recurrent lesions in recurrent or metastatic breast cancer patients.Methods Clinical and pathological data of 56 recurrent or metastatic breast cancer patients who were treated in Peking Union Medical College Hospital from January 2001 to February 2015 were retrospectively analyzed.The changes in the expressions of ER,PR,Cerb-B2,Ki-67 index,and P53 status were analyzed.Results The hormone receptor positive rate between primary tumor and recurrent or metastatic sites decreased from 60.7% to 57.1% for ER and from 55.4% to 44.6% for PR,respectively.Changes in hormone receptor status were seen at the rate of 12.5%(7/56)and 16.1%(9/56)for ER and PR,respectively.Cerb-B2 receptor positive rate increased from 19.1% to 29.5% and the discordance rate was 9.1%(4/44).The discordance rate of Ki-67 index was 24.5%(12/49).The P53 receptor positive rate increased from 37.5% to 55.6% and the discordance rate was 13.3%(6/45).Conclusion Although the relevant rules of above changes are still controversial,these findings still have great clinical significance for making effective treatment decisions of recurrent or metastatic breast cancer.

Pulmonary Bulla and Bilateral Diffusely-distributed Nodules: Report of One Case and Literature Review / 中国医学科学院学报

Lung cancer is mostly characterized by a pulmonary solid mass on CT. In rare cases,patients do not have these typical manifestation but present with diffusely-distributed small nodules and pulmonary bullae,which can easily be misdiagnosed. A special case of lung adenocarcinoma was managed in our hospital from September 24th to December 19th in 2016. Under high-resolution CT,multiple nodules were seen in both lungs,mostly in the upper lungs,involving the pleura and interlobular fissures. Some nodules had cystic changes. A large bulla was seen in the left upper lung. Its wall was thickened with multiple nodules. Lung adenocarcinoma was pathologically confirmed.

Expressions of Estrogen Receptor,Progestogen Receptor,Cerb-B2,and Ki67 Index in the Simple Mucinous Carcinoma of the Breast / 中国医学科学院学报

<p><b>OBJECTIVE</b>To approach the expressions of estrogen receptor (ER),progestogen receptor (PR),Cerb-B2,and Ki67 index in simple mucinous carcinoma of the breast and their clinical significance.</p><p><b>METHODS</b>The clinicopathological data of 72 patients with simple mucinous carcinoma of the breast who were treated in our hospital from 1997 to 2012 were retrospectively studied. Expressions of ER,PR,Cerb-B2,and Ki67 index and their relationship with clinical characteristics were analyzed.</p><p><b>RESULTS</b>Nine patients had lymph node metastasis. Expressions of ER,PR,and Cerb-B2 were 77.8%,69.4%,and 3.1%,respectively. The expressions of ER,PR,and Cerb-B2 showed no correlation with age,menstrual status,and axillary lymph node metastasis (P>0.05). The expression of ER was correlated with tumor diameter (P=0.008) while the expression of PR and Cerb-B2 showed no such correlation.</p><p><b>CONCLUSIONS</b>High ER or PR expression and low Cerb-B2 expression predict good prognosis in patients with simple mucinous carcinoma of the breast. Combined detection of ER,PR,Cerb-B2,and Ki67 index may help to improve the multidisciplinary management of simple mucinous carcinoma of the breast.</p>

Value of cardiac magnetic resonance imaging for the diagnosis of cardiac amyloidosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the clinical features and cardiac magnetic resonance imaging (CMR) characteristics of patients with endomyocardial biopsy (EMB)-proven cardiac amyloidosis (CA).</p><p><b>METHODS</b>EMB proven CA patients underwent CMR examination from September 2006 to December 2010 were included. The findings of clinical manifestation, electrocardiogram, echocardiography and CMR were analyzed.</p><p><b>RESULTS</b>Among the 18 patients with EMB verified CA, 5 patients underwent CMR. All 5 patients had heart failure symptoms and electrocardiogram was abnormal. Echocardiogram showed concentric left ventricular hypertrophy, granular appearance of the myocardium, left atrial enlargement and moderate to severe left ventricular diastolic dysfunction. CMR revealed increased thickness of the left ventricular wall (especially at the inter-ventricular septum), enlarged bilateral auricle, restricted left ventricular filling with normal or mild to moderate reduced systolic function. Pleural and pericardial effusions were observed in 2 patients. Abnormal late gadolinium enhancement (LGE) was detected in all 5 patients. CMR revealed different patterns of LGE. Left ventricular global subendocardial delayed gadolinium enhancement or transmural delayed gadolinium enhancement were found, and patients also showed line-, granular- or patchy-like enhancement. The degree and range of LGE paralleled the disease course and were consistent with electrocardiogram changes.</p><p><b>CONCLUSIONS</b>As a noninvasive diagnostic tool, CMR is valuable in the diagnosis of CA. For patients with clinical suspicion of CA, CMR could be a helpful diagnostic tool, especially in the hospitals where EMB is not available.</p>

Importance of endomyocardial biopsy in unexplained cardiomyopathy in China: a report of 53 consecutive patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although endomyocardial biopsy (EMB) plays a crucial role in the final diagnosis in patients with heart failure of unknown etiology, the invasive nature of this technique limits its clinical application in China. The purpose of this study was to evaluate the clinical application of EMB in diagnosing cardiomyopathy with unexplained etiologies in China.</p><p><b>METHODS</b>Fifty-three consecutive patients (38 males, age 14 - 67 years, median 43 years) were included in the study who were initially diagnosed as unexplained cardiomyopathy and under EMB biopsy in Peking Union Medical College Hospital from 2006 to 2009. The patients were clinically divided into four groups: dilated, hypertrophic, restrictive and unclassified cardiomyopathy. Biopsies were performed via right internal jugular vein with the use of the bioptome under fluoroscopic guidance. Three to five endomyocardial samples were taken from each patient for light microscopy examination and one sample for electron microscopy was taken if necessary. For each patient, an initial clinical diagnosis, an EMB diagnosis and a final diagnosis prior to discharge were established. All the data were compared and analyzed for the evaluation of clinical utility of EMB in China.</p><p><b>RESULTS</b>In 26 patients initially diagnosed with restrictive cardiomyopathy (RCM), the etiology of the condition was finally diagnosed using EMB in 15; including 13 amyloidosis and two eosinophilic myocarditis. We employed EMB in 19 patients clinically diagnosed as dilated cardiomyopathy and detected viral myocarditis in one patient, cardiac involvement due to polymyositis in four and doxorubicin-induced cardiomyopathy in one. In five patients with severe left ventricle hypertrophy undergoing EMB, one patient was diagnosed as autophagic vacuolar cardiomyopathy and one as mitochondrial disease. In the remaining three patients with unclassified cardiomyopathy, EMB revealed infiltration of eosinophils as the cause of atrial ventricular block in one patient. Final diagnoses were made in 24 of the total 53 patients (45%) based on the combination of EMB and clinical data. Transient atrial ventricular block in a patient with prior complete left bundle branch block was the only complication occurred during the procedures.</p><p><b>CONCLUSION</b>The clinical application of EMB is safe. The combination of EMB and clinical data produced a better understanding of the mechanisms behind the clinically diagnosed cardiomyopathy in China.</p>

Clinico-pathological evaluation of restrictive cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>restrictive cardiomyopathy (RCM) is characterized by impairment of ventricular filling during diastole with preserved systolic function. The clinical and histopathological profile on endomyocardial biopsy of 25 consecutive patients with RCM was analyzed in this study.</p><p><b>METHODS</b>twenty-five patients with diagnosis of RCM and underwent endomyocardial biopsy (EMB) were enrolled in the study. The clinical characteristics, electrocardiogram, serum chemistry, right heart catheter and cardiac pathology results were obtained.</p><p><b>RESULTS</b>heart failure symptom was present in all 25 patients and left ventricular size and function were normal or near normal while serum brain natriuretic peptide (577 pg/ml) was moderately elevated. Right atrial and ventricular end-diastolic as well as pulmonary capillary wedge pressures derived from right heart catheter examination were increased. Amyloid deposition were evidenced in 16 and eosinophilic myocarditis in 2 patients upon pathological examination of EMB. In the remaining 7 patients, 3 were diagnosed idiopathic RCM, 2 were diagnosed as amyloidosis by biopsy from non-cardiac tissue and etiology remained unknown in 2 patients. Thus, conclusive diagnosis was made on EMB samples in 84% (21/25) patients of RCM.</p><p><b>CONCLUSION</b>RCM may result from various local and systemic disorders. EMB is helpful for identifying the underlying etiology.</p>

Evaluation of HER2 gene expression status in breast cancer by fluorescence in-situ hybridization / 中华病理学杂志

<p><b>OBJECTIVE</b>To deduce the protocol, scoring criteria and interpretive guidelines for assessment of HER2 gene expression status by fluorescence in-situ hybridization (FISH) and to compare the results with those obtained by immunohistochemistry.</p><p><b>METHODS</b>The HercepTest kit from Dako Cytomation was employed for immunohistochemistry. FISH for HER2 gene expression status was performed using PathVysion DNA probe kit on the archival paraffin-embedded sections of breast cancer tissues from 28 Chinese female patients with immunohistochemical staining scores of (3 +), (2 +), (1 +) and 0.</p><p><b>RESULTS</b>Ten of the 12 patients with score (3 +) by immunohistochemistry were positive for HER2 by FISH, with 2 cases being polysomy. Two other cases with FISH-negative were also shown to be polysomy. Seven of the 10 patients with score (2 +) by immunohistochemistry showed HER2 gene amplification, with 1 case being polysomy. Two of the remaining 3 cases, which were FISH-negative, were shown to be polysomy. All the patients with scores (1 +, number = 3 ) or 0 ( number = 3) by immunohistochemistry failed to show amplification. One case of polysomy was noted in either group.</p><p><b>CONCLUSIONS</b>Immunohistochemistry is useful as an initial screening tool for HER2 expression status. Because of the obvious discrepancies between protein expression and gene amplification, patients with score (2 +) by immunohistochemistry should undergo FISH testing as well. FISH is also required in selected examples with score (3 +) immunohistochemical results, especially in those with false-positive immunohistochemistry due to chromosome 17 aneuploidy.</p>

Detection of Y chromosome loss by fluorescence in situ hybridization in pancreatic cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between loss of Y chromosome and development of pancreatic cancer.</p><p><b>METHOD</b>The status of Y chromosome was analyzed by two color interphase fluorescence in situ hybridization. performed on paraffin sections of pancreatic cancer tissues from 15 Chinese males. The probes located on the heterochromatin region of chromosome Y (maps to Yq12) and on the alpha satellite of X chromosome (maps to centromeric region) were selected for testing and as control respectively.</p><p><b>RESULTS</b>The cancer cells from 10 out of the 15 pancreatic cancer patients studied showed loss of chromosome Y. The Y chromosome in the cells of surrounding non-neoplastic pancreatic tissues was intact.</p><p><b>CONCLUSIONS</b>Loss of chromosome Y occurs non-randomly in tumor cells of Chinese male patients with pancreatic cancer. This cytogenetic aberration, which happens in high frequency, may serve as one of the markers for pancreatic malignancy.</p>